Human Inheritance: Patterns, Disorders, and Pedigrees

1. Ch 14 Human Inheritance • Human inheritance involves more issues than pea plants • Relatively few traits follow a Mendelian inheritance pattern, but we cannot ethically perform test crosses • Most human traits are polygenic • Influenced by multiple genes and can be influenced by environmental factors • Inheritance can be autosomal dominant, autosomal recessive, or sex-linked

2. Autosomal Dominance Pattern • Autosomal dominance pattern • Caused by ONE dominant allele • Those who do not have the disorder are homozygous recessive. • BB – Disease, Bb – Disease, bb – Normal • Trait appears in every generation • If one parent is heterozygous, and the other is homozygous recessive, each child has a 50% chance of inheriting the dominant allele

3. Autosomal Dominant Disorders • Achondroplasia: form of hereditary dwarfism caused by mutations in gene for a growth factor • 75% born to parents of average size • Hutchinson-Gilford Progeria: accelerated aging caused by mutation in gene for laminA • 1 in 4 million newborns worldwide • Huntington’s Disease: impacts brain cell function • No cure, but medications to cope with symptoms • People usually die 15-20 years after onset of degeneration

4. Autosomal Recessive Pattern • Two recessive alleles, one from each parent • If an individual is heterozygous, they are a carrier(they could pass it on even if they don’t have it!) • BB – Normal, Bb – Normal, but a carrier, bb – Disease • Often skips a generation • Each child of two carriers has a 25% chance of being homozygous

5. Autosomal Recessive Disorders • Tay-Sachs Disease: caused by mutation in enzyme that breaks down a particular type of lipid • 1 in 300 of general population carries the allele, 1 in 30 Jews of eastern European descent carries the allele • Buildup of fatty acids in brain, cherry red spot on back of eye, Causes deafness, blindness, severe retardation, and death usually by age 4 • Most carriers choose to avoid birth • Albinism: caused by mutations that reduce melanin synthesis

6. X-Linked Recessive Pattern • Also called SEX-linked • Allele is inherited on the X chromosome • Most are recessive because dominant alleles would be lethal to male embryos

7. X-Linked Recessive Pattern • X-linked recessive disorders tend to appear in men more often than women because they only have one X • Women have two (XX), so they can be heterozygous (carrier) for a recessive allele • Men can transmit an X-linked allele to daughters, but not to sons–only a woman can pass an X-linked allele to a son

8. X-Linked Recessive Disorders • Red-Green Colorblindness: confuse red and green colors; others see green as shades of gray, but perceive blues and yellows quite well • Duchenne Muscular Dystrophy: causes the protein dystrophin to be absent • Muscle and nerve cells become replaced by fat cells • Affects 1 in 3,500 people, mostly boys • Wheelchair by age 12, and die from a heart disorder or respiratory failure before age 30

9. X-Linked Recessive Disorders • Hemophilia: Disorders in which the blood does not clot properly • Males and homozygous females have prolonged bleeding • Affected people bruise easily, but internal bleeding is their most serious problem • Common in royal families of Europe and Russia during 19th century

10. Patricia is a healthy carrier of hemophilia, Sam is healthy. Complete the Punnett square below. • Mom’s genotype? Dad’s genotype? • What is the probability of getting: • Daughter with hemophilia? Son with hemophilia? Carrier? Healthy child? Judy is homozygous recessive for colorblindness and Dennis is healthy. Complete the Punnett square below. • Mom’s genotype? Dad’s genotype? • What is the probability of getting: • Colorblind daughter? Color blind son? Carrier? Heterozygous child?

11. Pedigrees • Geneticists often use historical records to study human traits • Pedigree: Diagram that traces the inheritance of a particular trait through several generations of the same family • Determine the probability that a trait will recur in future generations • Predict probability that a disorder will reappear

13. Pedigrees • Individuals are in birth order from left to right (oldest at left, youngest on right) • Individuals are numbered, Generations are numbered with roman numerals • When referring to an individual, use the generation number, then the individual number • II-4

14. Pedigrees • From a pedigree, you can tell whether a family carries an autosomal dominant/recessive disorder, or sex-linked disorder • Autosomal or Sex-linked: • Autosomal – shows in both sexes equally • Sex-linked – show mostly in males • Dominant or Recessive: • Dominant – every individual with trait has parent with trait • Recessive – individual with trait has parent without trait

16. Changes in Chromosome Number • Abnormal events can occur before/during meiosis causing a new individual to have the wrong chromosome number • Nondisjunction: Failure of sister chromatids or homologous chromosomes to separate during nuclear division • Changes in chromosome number are usually caused by nondisjunction • Affects chromosome number at fertilization and causes genetic disorders among resulting offspring

17. Changes in Chromosome Number

18. Changes in Chromosome Number • Polyploidy: Individuals have three or more of each type of chromosome • Lethal in humans, many flowering plants, and some insects, fishes, and other animals, are polyploidy • Aneuploidy: individual’s cells have too many or too few copies of a chromosome • Most cases of autosomal aneuploidy are lethal in embryos

19. Changes in Chromosome Number • Down Syndrome [Trisomy 21]: 3 copies of chromosome 21 • Mild to moderate mental impairment • Health problems such as heart disease • Flattened facial profile; fold of skin on inner corner of eye • Low muscle tone • Occurs in 1 in 700 births; risk increases with maternal age

20. Changes in Chromosome Number • Edward’s Syndrome - Trisomy 18: almost every organ system affected 1:10,000 live births. Children with full Trisomy 18 generally do not live more than a few months. • Patau Syndrome - Trisomy 13: serious eye, brain, circulatory defects as well as cleft palate. 1:5000 live births. Children rarely live more than a few months

21. Sex Chromosome Changes • Changes in sex chromosomes usually result in some degree of impairment in learning and motor skills • Turner Syndrome (XO): Well proportioned but short, Ovaries do not develop properly, Insufficient sex hormones to become sexually mature • XXX syndrome: Mild mental impairment, Usually no physical or medical problems • Klinefelter syndrome (XXY): Overweight and tall; normal intelligence, make more estrogen and less testosterone than normal males, which has feminizing effects • XYY Syndrome: Taller than average, mild mental impairment

22. Genetic Screening • Can estimate probability that a child will inherit a genetic disorder • Some disorders can be detected early enough to start countermeasures before symptoms develop • Testing of an embryo or fetus can reveal genetic abnormalities or disorders before birth • Obstetric sonography, Fetoscopy, Amniocentesis, Chorionic villus sampling (CVS)

23. Genetic Testing • You can have your own genes tested to determine if you carry specific genes • Though you may carry a certain gene, many traits arise from a complex interplay of your genes and your environment • Angelina Jolie discovered she carried the BRCA1 mutation associated with an 87% lifetime risk of developing breast cancer • You could carry an allele for Alzheimer’s however it is only a risk, there is no guarantee you will develop the disease

24. CH 15 Genome • Genome:an organism’s entire set of genetic material, consists of thousands of genes • A genomic library collectively contains all DNA in a genome • The human genome consists of about 3 billion nucleotide bases • 50 years after discovery of DNA structure, sequencing of the human genome was complete [2003]

25. Genomics • Genomics: The study of whole-genome structure and function • First human genome sequence took 15 years; takes about a day now • Whole-genome comparisons can provides insights into evolution and medical benefits • We have learned the function of human genes by studying counterpart genes in other species

26. Genomics • Your genome remains constant, however gene expression is not • About 99% [~2.97 billion nucleotides] of your DNA is the same as everyone else’s, the differences [~30 million nucleotides] make you unique • Most alleles for a gene differ by only one nucleotide, which is the basis of variation in human traits • DNA Profiling: Identifies a person by their DNA • “DNA fingerprint profile” in criminal investigation

27. Genetic Engineering • Genetic Engineering: Process by which an individual’s genome is deliberately modified [changed] • Produces a genetically modified organism (GMO) • A gene may be altered or reinserted within the same species • Transferring a gene from one species to another (transgenic) • GM plants are engineered for drought tolerance, resistance to diseases, and added nutrition

28. Genetic Engineering • GM microorganisms make enzymes that slow the staling of bread or improve the taste of juice • GM animals include goats that make proteins to treat cystic fibrosis, heart attacks, and clotting disorders, pigs with heart-healthy fat and lower phosphate feces, faster growing salmon, and farm animals that produce more meat or milk

29. Editing Genomes • Gene therapy: Gene is transferred into body cells to correct a genetic defect or treat a disease • Tested as a treatment for heart attack, sickle-cell anemia, cystic fibrosis, hemophilia A, Parkinson’s and Alzheimer’s diseases, several cancers, and inherited diseases • Designer Babies: using genetic engineering to choose the traits of your offspring • Savior Siblings: children conceived with the initial purpose of acting as donors for a sick brother or sister.

30. Biotechnology • Biotechnology: technical manipulation of application of biological systems • Breeding: the bringing together of two living things to produce offspring • Selective breeding: can bring out the desired traits of living things • examples: dog breeding, agriculture, hybridization • Inbreeding: process in which closely related organisms are bred to ensure inheritance of desired traits and elimination of undesired traits • Can be harmful, inheritance of recessive traits

31. Cloning DNA • Restriction Enzymes: cut DNA at a specific nucleotide sequence creating manageable DNA chunks • Recombinant DNA: combines segments of DNA from different sources • DNA from two sources cut into fragments; leaves “sticky ends,” fragments are mixed, matching sticky ends base pair with each other, DNA ligase seals the base-paired DNA fragments • DNA cloning mass produces specific DNA fragments and a huge population of clones can be grown

32. Biotechnology • DNA sequencing allows us to determine the order of nucleotides in a molecule of DNA • Gel Electrophoresis: electric current is used to separate DNA fragments according to size • Electric field pulls DNA fragments through gel, fragments of different sizes move at different rates (shorter moves through faster) • Fragments of the same length gather into bands

33. CRISPR • Powerful new method for editing chromosomal DNA • RNA guides a restriction enzyme to a piece of DNA, the enzyme cuts the DNA at that a certain spot • A new piece of DNA is put there to repair the break • Most important part is the RNA and DNA can be designed to precisely target and change and essential part of the genome • HIV could be edited out of a person’s cells to prevent relapse • Mutations could be removed to cure genetic disorders

34. https://www.youtube.com/watch?v=jAhjPd4uNFY#action=sh

35. Concerns with Altering Genomes • Concern that altering genomes in any way has us on a slippery slope that may result in irreversible damage to ourselves and to the biosphere • An oversight could, for example, deliver unwanted genetic modifications into humans